Metachromatic leukodystrophy: consequences of sulphatide accumulation
Metachromatic leukodystrophy: consequences of sulphatide accumulation
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DOI：
10.1080/08035320310000528
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发表时间：
2003-12-01
期刊：
影响因子：
3.8
通讯作者：
Schaeren-Wiemers, N
中科院分区：
文献类型：
--
作者：
Gieselmann, V;Franken, S;Schaeren-Wiemers, N
异染性脑白质营养不良是一种溶酶体脂质沉积症。它是由芳基硫酸酯酶A基因突变引起的，芳基硫酸酯酶A是一种参与鞘脂3 '-O-磺基半乳糖神经酰胺（硫苷脂）降解的酶。这种膜脂质可以在各种细胞类型中发现，但在神经系统的髓鞘中浓度特别高。由于硫苷脂的积累，患者遭受进行性的、最终致命的脱髓鞘。在神经系统中，脂质储存不仅影响少突胶质细胞，而且影响神经元，此外，导致星形胶质细胞增生和小胶质细胞活化。在细胞水平上，溶酶体硫酸盐储存也影响髓鞘本身的脂质组成，并对特定髓鞘膜相关蛋白的量和定位产生影响。在这里，我们回顾数据，主要是基于芳基硫酸酯酶A基因敲除小鼠模型的异染性脑白质营养不良。结论：异染性脑白质营养不良的基因敲除小鼠模型提供了深入了解的组织病理学和细胞后果的硫苷脂存储。
Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide). This membrane lipid can be found in various cell types, but in particularly high concentrations in the myelin of the nervous system. Patients suffer from progressive, finally lethal, demyelination due to accumulation of sulphatide. In the nervous system, lipid storage not only affects oligodendrocytes but also neurons and, in addition, leads to astrogliosis and activation of microglia. At the cellular level, lysosomal sulphatide storage also affects the lipid composition of myelin itself and has consequences for the amount and localization of particular myelin membrane-associated proteins. Here we review data, largely based on an arylsulphatase A knock-out mouse model of metachromatic leukodystrophy.Conclusion: The knock-out mouse model of metachromatic leukodystrophy has provided insights into the histopathological and cellular consequences of sulphatide storage.